CLINICAL AND IMMUNE-RESPONSES IN ADVANCED COLORECTAL-CANCER PATIENTS TREATED WITH ANTIIDIOTYPE MONOCLONAL-ANTIBODY VACCINE THAT MIMICS THE CARCINOEMBRYONIC ANTIGEN

Carcinoembryonic antigen (CEA) is expressed in a wide variety of adeno carcinomas, and it is well recognized that cancer patients are immunol ogically ''tolerant'' to CEA, The purpose of this study was to determi ne whether we could break immune tolerance to CEA by vaccinating patie nts with a monoclonal anti-idiotype antibody that is the internal imag e of CEA and to determine what impact this might have on patient survi val, Twenty-four patients with advanced CEA-positive colorectal cancer who failed standard therapies except for two mere entered into this P hase Ib trial, One patient was considered not assessable, because on t he day of entering into the study, she was diagnosed with acute myelog enous leukemia, Patients were treated with 1, 2, or 4 mg of aluminum h ydroxide-precipitated 3H1 anti-idiotype antibody every other week for four injections and then monthly until tumor progression was observed, Immunological monitoring included humoral and cellular idiotypic and CEA responses, and all patients were evaluated for toxicity, response, and survival, Hyperimmune sera from 17 of 23 patients demonstrated an anti-anti-idiotypic Ab3 response, and 13 of these responses were demo nstrated to be true anti-CEA responses (Ab1'), The antibody response w as polyclonal, and 11 mediated antibody-dependent cellular cytotoxicit y. Ten patients had idiotypic T-cell responses, and five had specific T-cell responses to CEA, None of the patients had objective clinical r esponses, but overall median survival for the 23 evaluable patients wa s 11.3 months, with 44% 1-year survival (95% confidence interval, 23-6 4%), Toxicity was limited to local swelling and minimal pain, Anti-idi otype monoclonal antibody 3H1 that mimics CEA was able to break immune tolerance in the majority of treated patients, Overall survival of 11 .3 months was comparable to other phase II data with advanced colorect al cancer patients treated with a variety of chemotherapy agents, incl uding irinotecan, with considerably less toxicity, Although it is not clear that the vaccine itself had an impact on survival, this should b e determined in a Phase III randomized trial.